This invention is related to the repair, reconstruction and protection of tissue using compositions containing flavonoids and/or flavonols.
It has been known that phenolic compounds, including flavonoids and flavonols, have anti-inflammatory properties. It has been known that several flavonones, flavonols, isoflavonones and catechins, can inhibit the proliferation of inflammatory (granulation) tissue. These agents can decrease capillary permeability and strengthen the blood vessel wall, thus preventing vascular fragility. The agents have been shown to have affinity for and enhance synthesis of connective tissue.
Some flavonoids have been found to stimulate collagen and elastin cross-linking. It is believed that proline hydroxylation and modulation of polysaccharide production and function may be among the mechanisms by which benefit occurs. However, bioaction of these compounds, when given alone, is inadequate to provide desired clinical results. It is necessary to find more effective means of delivering clinical benefits that can arise from exposure to flavonoids.
Glucosamine and/or glucosamine sulfate used in conjunction with chondroitin have been used previously to treat diseases arising from pathological changes (for example, osteoarthritis) in joints for purposes of reducing pain and increasing mobility. Clinical improvement in motion and reduction of pain are reported. However, the time required to achieve reduction in pain is measured in months and the improvement in mobility is usually modest. For example, four to sixteen weeks is usually needed before measurable reduction in pain is observed. Mobility improvements in the range of only 1:5 to twenty-five degrees are achieved. While such improvement is helpful, the long period of time required to achieve benefit results in voluntary ceasation of treatment in many patients. There is need for means of treatment that will provide noticeable improvement in joint comfort and function in a shorter time period.
Ascorbic acid (vitamin C), its salts and esters (hereinafter often referred to as ascorbate), have frequently been used to augment the vitamin C usually found in the diet. Ascorbates have been known to be essential to collagen formation and to maintenance of the integrity of structures of mesenchymal origin. Ascorbates have been given both systemically and topically to enhance wound healing and are necessary for utilization of folate, a B vitamin. Vitamin C facilitates absorption of iron and is necessary to the utilization of folic acid ingested in the diet. Potassium, calcium, magnesium and/or zinc ascorbates are useful reducing substances that stimulate connective tissue synthesis, have steroid-sparing effects, and act as biological reducing agents. Thereby, ascorbate enhances detoxification of a variety of environmental toxins from nitrosamines to chlorinated heterocyclic pseudoestrogens. There is a need for properly balanced ascorbate forms which can provide improved benefit.
It is the purpose of this invention to provide increased benefit from known agents by providing simultaneous administration of agents, which have previously been given separately for differing purposes, in order to obtain synergistic effects from the combinations taught and claimed herein. The administration of flavonols and/or flavonoids in conjunction with compositions containing vitamin C and/or salts and esters of vitamin C provides advantageous sparing of autocoids (internal steroids). The simultaneous administration of flavonols and/or flavonoids to compositions containing glucosamine and or glucosamine sulfate and chondroitin stimulates rapid improvement in joint function. The addition to the flavonoids and/or flavonols to previously administered compositions is a most convenient method of achieving enhanced benefits.
The use of combinations of flavonoids and flavonols for use in relieving pain is also a part of the invention. The reliance on flavonoids and flavonols for relief of pain whilst avoiding use of non-sterolidal anti-inflammatory drugs (NSAIDs) was not previously considered.
Administration of compositions containing glucosamine and/or glucosamine sulfate and chondroitin in conjunction with flavonols and/or flavonoids provides decrease in discomfort and increase in mobilitylin patients with degenerative joint conditions. Such improvement is not seen when only the glucosamine and/or glucosamine sulfate and chondroitin are administered or when only flavonoids in combination with flavonols is given. As seen in Example 1, the combination of the invention offers much improved treatment modality to patients suffering from degenerative processes such as osteoarthritis/osteoarthrosis.
When the cause of discomfort results from trauma to otherwise healthy tissue, it is appropriate to administration of flavonoid/flavonol compositions (without glucosamine/glucosamine sulfate) to relieve the pain and inflammation. The pain reduction afforded by the combination is comparable to or better than that achieved with non-steroidal anti-inflammatory drugs (NSAIDs). It has also been noted that the addition of manganese (specifically) appears to further increase the benefit afforded from the compositions, as is exemplified below. It was not previously known that the use of flavonoid/flavonol compositions could be relied on for relief of pain.
The flavonols and flavonoids are available from many natural sources. Those exemplified in the compositions were obtained from Ashland Chemical Company, Ashland, Oreg. The flavonols used in the particular examples were extracted from pine bark or grape seeds. The flavonoids were extracted from S. japonica. 
The balanced potassium, calcium, magnesium and zinc ascorbates are prepared by reacting the respective potassium, calcium, magnesium and zinc soluble carbonates with ascorbic acid. (The ascorbic acid was obtained from Takeda, Inc and Merck.
The glucosamine and glucosamine sulfate are available from Seltzer Chemical Co or ZetaPharm, Inc.